Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits ( Olea europaea

Absorption, metabolism, and excretion of 3,4-DHPEA-EDA, oleuropein, and hydroxytyrosol isolated from olive fruits were newly evaluated after oral and intravenous administration in freely moving rats cannulated in the portal vein, jugular vein, and bile duct. Orally administered 3,4-DHPEA-EDA, an important bioactive compound in olive pomace, was readily absorbed and metabolized to hydroxytyrosol, homovanillic acid, and homovanillyl alcohol, as shown by dose-normalized 4 h area under the curve (AUC0→4 h/Dose) values of 27.7, 4.5, and 4.2 μM·min·kg/μmol, respectively, in portal plasma after oral administration. The parent compound 3,4-DHPEA-EDA was not observed in the portal plasma, urine, and bile after oral and intravenous administration. Additionally, hydroxytyrosol, homovanillic acid, and homovanillyl alcohol in the portal plasma after oral administration of hydroxytyrosol showed 51.1, 22.8, and 7.1 μM·min·kg/μmol AUC0→4 h/Dose, respectively. When oleuropein, a polar glucoside, was injected orally, oleuropein in the portal plasma showed 0.9 μM·min·kg/μmol AUC0→4 h/Dose. However, homovanillic acid was detected from oleuropein in only a small amount in the portal plasma. Moreover, the bioavailability of hydroxytyrosol and oleuropein for 4 hours was 13.1% and 0.5%, respectively. Because the amount of 3,4-DHPEA-EDA in olive fruits is about 2-3 times greater than that of hydroxytyrosol, the metabolites of 3,4-DHPEA-EDA will influence biological activities

Aromatic oil from lavender as an atopic dermatitis suppressant

In atopic dermatitis (AD), nerves are abnormally stretched near the surface of the skin, making it sensitive to itching. Expression of neurotrophic factor Artemin (ARTN) involved in such nerve stretching is induced by the xenobiotic response (XRE) to air pollutants and UV radiation products. Therefore, AD can be monitored by the XRE response. Previously, we established a human keratinocyte cell line stably expressing a NanoLuc reporter gene downstream of XRE. We found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan metabolite and known inducer of the XRE, increased reporter and Artemin mRNA expression, indicating that FICZ-treated cells could be a model for AD. Lavender essential oil has been used in folk medicine to treat AD, but the scientific basis for its use is unclear. In the present study, we investigated the efficacy of lavender essential oil and its major components, linalyl acetate and linalool, to suppress AD and sensitize skin using the established AD model cell line, and keratinocyte and dendritic cell activation assays. Our results indicated that lavender essential oil from L. angustifolia and linalyl acetate exerted a strong AD inhibitory effect and almost no skin sensitization. Our model is useful in that it can circumvent the practice of using animal studies to evaluate AD medicines

Juvenile hormone synthesis and signaling disruption triggering male offspring induction and population decline in cladocerans (water flea): Review and adverse outcome pathway development

Juvenile hormone (JH) are a family of multifunctional hormones regulating larval development, molting, metamorphosis, reproduction, and phenotypic plasticity in arthropods. Based on its importance in arthropod life histories, many insect growth regulators (IGRs) mimicking JH have been designed to control harmful insects in agriculture and aquaculture. These JH analogs (JHAs) may also pose hazards to nontarget species by causing unexpected endocrine-disrupting (ED) effects such as molting and metamorphosis defects, larval lethality, and disruption of the sexual identity. This critical review summarizes the current knowledge of the JH-mediated effects in the freshwater cladoceran crustaceans such as Daphnia species on JHA-triggered endocrine disruptive outputs to establish a systematic understanding of JHA effects. Based on the current knowledge, adverse outcome pathways (AOPs) addressing the JHA-mediated ED effects in cladoceran leading to male offspring production and subsequent population decline were developed. The weight of evidence (WoE) of AOPs was assessed according to established guidelines. The review and AOP development aim to present the current scientific understanding of the JH pathway and provide a robust reference for the development of tiered testing strategies and new risk assessment approaches for JHAs in future ecotoxicological research and regulatory processes.publishedVersionacceptedVersio

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Microglial re-modeling contributes to recovery from ischemic injury of rat brain: A study using a cytokine mixture containing granulocyte-macrophage colony-stimulating factor and interleukin-3

Ischemic stroke is a leading cause of mortality and permanent disability. Chronic stroke lesions increase gradually due to the secondary neuroinflammation that occurs following acute ischemic neuronal degeneration. In this study, the ameliorating effect of a cytokine mixture consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 was evaluated on ischemic brain injury using a rat stroke model prepared by transient middle cerebral artery occlusion (tMCAO). The mixture reduced infarct volume and ameliorated ischemia-induced motor and cognitive dysfunctions. Sorted microglia cells from the ischemic hemisphere of rats administered the mixture showed reduced mRNA expression of tumor necrosis factor (TNF)-α and IL-1β at 3 days post-reperfusion. On flow cytometric analysis, the expression of CD86, a marker of pro-inflammatory type microglia, was suppressed, and the expression of CD163, a marker of tissue-repairing type microglia, was increased by the cytokine treatment. Immunoblotting and immunohistochemistry data showed that the cytokines increased the expression of the anti-apoptotic protein Bcl-xL in neurons in the ischemic lesion. Thus, the present study demonstrated that cytokine treatment markedly suppressed neurodegeneration during the chronic phase in the rat stroke model. The neuroprotective effects may be mediated by phenotypic changes of microglia that presumably lead to increased expression of Bcl-xL in ischemic lesions, while enhancing neuronal survival

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration

(1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. The mean +/- SD in BV was 4.38 +/- 0.88 l (n = 25) and 4.69 +/- 1.11 l (n = 26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n = 26) and 4.48 +/- 0.86 l (n = 25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometr

Raman Molecular Fingerprints of Rice Nutritional Quality and the Concept of Raman Barcode

The nutritional quality of rice is contingent on a wide spectrum of biochemical characteristics, which essentially depend on rice genome, but are also greatly affected by growing/environmental conditions and aging during storage. The genetic basis and related identification of genes have widely been studied and rationally linked to accumulation of micronutrients in grains. However, genetic classifications cannot catch quality fluctuations arising from interannual, environmental, and storage conditions. Here, we propose a quantitative spectroscopic approach to analyze rice nutritional quality based on Raman spectroscopy, and disclose analytical algorithms for the determination of: (i) amylopectin and amylose concentrations, (ii) aromatic amino acids, (iii) protein content and structure, and (iv) chemical residues. The proposed Raman algorithms directly link to the molecular composition of grains and allow fast/non-destructive determination of key nutritional parameters with minimal sample preparation. Building upon spectroscopic information at the molecular level, we newly propose to represent the nutritional quality of labeled rice products with a barcode specially tailored on the Raman spectrum. The Raman barcode, which can be stored in databases promptly consultable with barcode scanners, could be linked to diet applications (apps) to enable a rapid, factual, and unequivocal product identification based on direct molecular screening

Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment

The Double Chooz Experiment presents an indication of reactor electron antineutrino disappearance consistent with neutrino oscillations. A ratio of 0.944 $\pm$ 0.016 (stat) $\pm$ 0.040 (syst) observed to predicted events was obtained in 101 days of running at the Chooz Nuclear Power Plant in France, with two 4.25 GW$_{th}$ reactors. The results were obtained from a single 10 m$^3$ fiducial volume detector located 1050 m from the two reactor cores. The reactor antineutrino flux prediction used the Bugey4 measurement as an anchor point. The deficit can be interpreted as an indication of a non-zero value of the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate of the prompt positrons and their energy spectrum we find \sang = 0.086 $\pm$ 0.041 (stat) $\pm$ 0.030 (syst), or, at 90% CL, 0.015 $<$ \sang $\ <$ 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments

Epidemiologic trends and distributions of imported infectious diseases among travelers to Japan before and during the COVID-19 pandemic, 2016 to 2021: a descriptive study

BACKGROUND: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the COVID-19 pandemic. This article aimed to describe those among travelers to Japan. METHODS: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020). RESULTS: A total of 3524 imported infectious disease cases were diagnosed during the study period, including 3439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95%CI, 41.5-78.7), malaria (21.7; 10.5-33.0), and typhoid fever (9.3; 1.9-16.8). CONCLUSION: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance